It is known in the art that both the amino and the hydroxy group are ortho and para directing. It is also known that when both groups are on an aryl ring, substitution reactions generally lead to a mixture of ortho and para isomers, and frequently to polysubstituted products. Needless to say, the formation and separation of isomeric mixtures greatly reduces product yields. For example, the synthesis of 2-amino-5-methylphenol involves only two reaction steps: (1) nitration of 3-methylphenol (meta-cresol) and (2) reduction of the nitro intermediate. However, the overall yield is very poor (less than 30%), due to the formation of other nitro isomers and the need to separate this mixture by steam distillation.
It is known in the art that 5-substituted-2-aminophenols are useful intermediates, for example, in the photographic industry. Unfortunately, this type of compound is generally hard to make in pure form and in good yield, for the reasons stated above.
As stated more fully below, one co-applicant herein has already provided a facile method for making a type of 5-substituted-2-aminophenols, and in a prior patent disclosed that the compounds are useful in the photographic arts. Although the compounds and process of this invention can be considered to be analogous to such prior compounds and processes, the present invention is unique from several viewpoints. First, it comprises a method for producing a desired compound substantially free from unwanted isomeric by-products. Second, the products of this invention can be produced in high yield, e.g., greater than 85%. Third, it provides a one-step introduction of a functional carboxy group or an aromatic ring containing functional or functionalizable groups into the 2-aminophenols or 3-aminophenols. To introduce these same substituents by established methods would require multistep reaction sequences and tedious separation of the resulting isomeric mixtures.
The problems faced by the Applicants were twofold. The first problem was the provision of a method for preparing derivatives of 2-aminophenols and 3-aminophenols in which a substituent group is directed to the position para to the amino group. As pointed out above, this is a difficult problem because of the presence of the powerfully directing hydroxy group bonded to the aromatic nucleus. The second problem was the provision of new compounds in which the para substituent has functionality which makes it possible to undergo further chemical reaction with other species to form new compounds. This part of the problem was also formidable because of the lack of precedence in the art. The task became even more difficult when, during the course of Applicants' investigations, it was demonstrated that seemingly related reactants failed to react, or yielded an entirely different product.
Applicants' invention solves both problems mentioned above. Furthermore, it provides a simple, one-step synthesis to compounds not previously known, and which are useful for preparing other chemicals of significant interest in the photographic and other arts. Thus, this invention is considered to be a significant advance in synthetic organic chemistry.